Human lung and skin fibroblasts are proving excellent models for the study of prostaglandin synthesis. Prostaglandin (PG) production by these cells is highly responsive to bradykinin, ascorbic acid and fetal bovine serum and very dependent on the growth state of the cell and on its aging level. We find that the above mentionaed effectors determine PG synthesis via either the release of the fatty acid precursor or through hydroperoxide-oxygen radical formation. Our goals are to elucidate these controls of PG synthesis and relate them to what occurs during cellular aging and cell replication. Studies will include determining the arachidonic acid composition of lipids in these cells, the release of arachidonic acid, the functions of cycloxygenase-peroxidase and the individual PG synthetases and the role of hydroperoxide compunds and oxygen radicals in PG production.